tbuckley/cabot-search huggingface dataset:
Mendelian randomization and pathway analysis demonstrate shared genetic associations between lupus and coronary artery disease
Authors: Jessica Kain, Katherine A. Owen, Miranda C. Marion, Carl D. Langefeld, Amrie C. Grammer, Peter E. Lipsky
Journal: Cell Reports Medicine (2022)

Coronary artery disease (CAD) is a leading cause of death in patients with systemic lupus erythematosus (SLE). Despite clinical evidence supporting an association between SLE and CAD, pleiotropy-adjusted genetic association studies are limited and focus on only a few common risk loci. Here, we identify a net positive causal estimate of SLE-associated non-HLA SNPs on CAD by traditional Mendelian randomization (MR) approaches. Pathway analysis using SNP-to-gene mapping followed by unsupervised clustering based on protein-protein interactions (PPIs) identifies biological networks composed of positive and negative causal sets of genes. In addition, we confirm the casual effects of specific SNP-to-gene modules on CAD using only SNP mapping to each PPI-defined functional gene set as instrumental variables. This PPI-based MR approach elucidates various molecular pathways with causal implications between SLE and CAD and identifies biological pathways likely causative of both pathologies, revealing known and novel therapeutic interventions for managing CAD in SLE.
Extracorporeal Membrane Oxygenation in the Therapy of Cardiogenic Shock: Results of the ECMO-CS Randomized Clinical Trial
Authors: Petr Ostadal, Richard Rokyta, Jiri Karasek, Andreas Kruger, Dagmar Vondrakova, Marek Janotka, Jan Naar, Jana Smalcova, Marketa Hubatova, Milan Hromadka, Stefan Volovar, Miroslava Seyfrydova, Jiri Jarkovsky, Michal Svoboda, Ales Linhart, Jan Belohlavek
Journal: Circulation (2022)

Background: Veno-arterial extracorporeal membrane oxygenation (VA-ECMO) is increasingly being used for circulatory support in patients with cardiogenic shock, although the evidence supporting its use in this context remains insufficient. The ECMO-CS trial (Extracorporeal Membrane Oxygenation in the Therapy of Cardiogenic Shock) aimed to compare immediate implementation of VA-ECMO versus an initially conservative therapy (allowing downstream use of VA-ECMO) in patients with rapidly deteriorating or severe cardiogenic shock. Methods: This multicenter, randomized, investigator-initiated, academic clinical trial included patients with either rapidly deteriorating or severe cardiogenic shock. Patients were randomly assigned to immediate VA-ECMO or no immediate VA-ECMO. Other diagnostic and therapeutic procedures were performed as per current standards of care. In the early conservative group, VA-ECMO could be used downstream in case of worsening hemodynamic status. The primary end point was the composite of death from any cause, resuscitated circulatory arrest, and implementation of another mechanical circulatory support device at 30 days. Results: A total of 122 patients were randomized; after excluding 5 patients because of the absence of informed consent, 117 subjects were included in the analysis, of whom 58 were randomized to immediate VA-ECMO and 59 to no immediate VA-ECMO. The composite primary end point occurred in 37 (63.8%) and 42 (71.2%) patients in the immediate VA-ECMO and the no early VA-ECMO groups, respectively (hazard ratio, 0.72 [95% CI, 0.46–1.12]; P =0.21). VA-ECMO was used in 23 (39%) of no early VA-ECMO patients. The 30-day incidence of resuscitated cardiac arrest (10.3.% versus 13.6%; risk difference, –3.2 [95% CI, –15.0 to 8.5]), all-cause mortality (50.0% versus 47.5%; risk difference, 2.5 [95% CI, –15.6 to 20.7]), serious adverse events (60.3% versus 61.0%; risk difference, –0.7 [95% CI, –18.4 to 17.0]), sepsis, pneumonia, stroke, leg ischemia, and bleeding was not statistically different between the immediate VA-ECMO and the no immediate VA-ECMO groups. Conclusions: Immediate implementation of VA-ECMO in patients with rapidly deteriorating or severe cardiogenic shock did not improve clinical outcomes compared with an early conservative strategy that permitted downstream use of VA-ECMO in case of worsening hemodynamic status. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT02301819.
Estrogen-related receptor alpha drives mitochondrial biogenesis and resistance to neoadjuvant chemoradiation in esophageal cancer
Authors: Mark P.G. Dings, Amber P. van der Zalm, Sanne Bootsma, Tatum F.J. van Maanen, Cynthia Waasdorp, Tom van den Ende, Dajia Liu, Peter Bailey, Jan Koster, Danny A. Zwijnenburg, C. Arnold Spek, Jan P.G. Klomp, Arthur Oubrie, Gerrit K.J. Hooijer, Sybren L. Meijer, Mark I. van Berge Henegouwen, Maarten C. Hulshof, Jacques Bergman, Cesar Oyarce, Jan Paul Medema, Hanneke W.M. van Laarhoven, Maarten F. Bijlsma
Journal: Cell Reports Medicine (2022)

Neoadjuvant chemoradiotherapy (nCRT) improves outcomes in resectable esophageal adenocarcinoma (EAC), but acquired resistance precludes long-term efficacy. Here, we delineate these resistance mechanisms. RNA sequencing on matched patient samples obtained pre-and post-neoadjuvant treatment reveal that oxidative phosphorylation was the most upregulated of all biological programs following nCRT. Analysis of patient-derived models confirms that mitochondrial content and oxygen consumption strongly increase in response to nCRT and that ionizing radiation is the causative agent. Bioinformatics identifies estrogen-related receptor alpha (ESRRA) as the transcription factor responsible for reprogramming, and overexpression and silencing of ESRRA functionally confirm that its downstream metabolic rewiring contributes to resistance. Pharmacological inhibition of ESRRA successfully sensitizes EAC organoids and patient-derived xenografts to radiation. In conclusion, we report a profound metabolic rewiring following chemoradiation and demonstrate that its inhibition resensitizes EAC cells to radiation. These findings hold broader relevance for other cancer types treated with radiation as well.
Perspective on a chemistry classification system for AI-assisted formulation development
Authors: Michael B Bolger
Journal: Journal of Controlled Release (2022)

This perspective article draws a distinction between some of the well-known drug classification systems and a "Chemistry Classification System" (CCS). Rather than have drug classification based on some simple properties like solubility and permeability or route of systemic elimination, a CCS results in more than four or five classes and each class has distinct properties that impact formulation development. This perspective provides and outline of 13 classes, but a CCS is a flexible system that introduces a thought process for classification. The number of classes is not rigid, and chemists are encouraged to adapt these methods to their own situations. A CCS utilizes machine-learning models and artificial intelligence (AI) to estimate physicochemical properties that result in unique, frequently observed dissolution, Absorption, Distribution, Metabolism, and Excretion (ADME) properties to guide formulation development.
Time to Treatment in ST-Segment Elevation Myocardial Infarction
Authors: Andrew S. Oseran, Robert W. Yeh
Journal: JAMA (2022)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Association of post‐vaccination adverse reactions after influenza vaccine with mortality and cardiopulmonary outcomes in patients with high‐risk cardiovascular disease: the <scp>INVESTED</scp> trial
Authors: Alexander Peikert, Brian L. Claggett, KyungMann Kim, Jacob A. Udell, Jacob Joseph, Akshay S. Desai, Michael E. Farkouh, Sheila M. Hegde, Adrian F. Hernandez, Deepak L. Bhatt, J. Michael Gaziano, H. Keipp Talbot, Clyde Yancy, Inder Anand, Lu Mao, Lawton S. Cooper, Scott D. Solomon, Orly Vardeny
Journal: European Journal of Heart Failure (2022)
How T-lymphoblastic leukemia can be classified based on genetics using standard diagnostic techniques enhanced by whole genome sequencing
Authors: Janine Müller, Wencke Walter, Claudia Haferlach, Heiko Müller, Irene Fuhrmann, Martha-Lena Müller, Henning Ruge, Manja Meggendorfer, Wolfgang Kern, Torsten Haferlach, Anna Stengel
Journal: Leukemia (2022)
Non-coding variants disrupting a tissue-specific regulatory element in HK1 cause congenital hyperinsulinism
Authors: Matthew N. Wakeling, Nick D. L. Owens, Jessica R. Hopkinson, Matthew B. Johnson, Jayne A. L. Houghton, Antonia Dastamani, Christine S. Flaxman, Rebecca C. Wyatt, Thomas I. Hewat, Jasmin J. Hopkins, Thomas W. Laver, Rachel van Heugten, Michael N. Weedon, Elisa De Franco, Kashyap A. Patel, Sian Ellard, Noel G. Morgan, Edmund Cheesman, Indraneel Banerjee, Andrew T. Hattersley, Mark J. Dunne, Ivo Barić, Liat de Vries, Samar S. Hassan, Khadija Nuzhat Humayun, Floris Levy-Khademi, Catarina Limbert, Birgit Rami-Merhar, Verónica Mericq, Kristen Neville, Yasmine Ouarezki, Ana Tangari, Charles Verge, Esko Wiltshire, Sarah J. Richardson, Sarah E. Flanagan
Journal: Nature Genetics (2022)
Clinical experience with use of oral Tecovirimat or Intravenous Cidofovir for the treatment of Monkeypox in an Italian reference hospital
Authors: Annalisa Mondi, Roberta Gagliardini, Valentina Mazzotta, Serena Vita, Fabrizio Carletti, Carmela Pinnetti, Maria Letizia Giancola, Eliana Specchiarello, Simone Lanini, Francesca Faraglia, Claudia Minosse, Jessica Paulicelli, Andrea Mariano, Gabriella Rozera, Carla Fontana, Paolo Faccendini, Fabrizio Maggi, Enrico Girardi, Francesco Vaia, Emanuele Nicastri, Andrea Antinori
Journal: Journal of Infection (2022)
The landscape of hervRNAs transcribed from human endogenous retroviruses across human body sites
Authors: Jianqi She, Minghao Du, Zhanzhan Xu, Yueqi Jin, Yu Li, Daoning Zhang, Changyu Tao, Jian Chen, Jiadong Wang, Ence Yang
Journal: Genome biology (2022)

Abstract Background Human endogenous retroviruses (HERVs), the remnants of ancient retroviruses, account for 8% of the human genome, but most have lost their transcriptional abilities under physiological conditions. However, mounting evidence shows that several expressed HERVs do exert biological functions. Here, we systematically characterize physiologically expressed HERVs and examine whether they may give insight into the molecular fundamentals of human development and disease. Results We systematically identify 13,889 expressed HERVs across normal body sites and demonstrate that they are expressed in body site-specific patterns and also by sex, ethnicity, and age. Analyzing cis -ERV-related quantitative trait loci, we find that 5435 hervRNAs are regulated by genetic variants. Combining this with a genome-wide association study, we elucidate that the dysregulation of expressed HERVs might be associated with various complex diseases, particularly neurodegenerative and psychiatric diseases. We further find that physiologically activated hervRNAs are associated with histone modifications rather than DNA demethylation. Conclusions Our results present a locus-specific landscape of physiologically expressed hervRNAs, which represent a hidden layer of genetic architecture in development and disease.
Deep label fusion: A generalizable hybrid multi-atlas and deep convolutional neural network for medical image segmentation
Authors: Long Xie, Laura E.M. Wisse, Jiancong Wang, Sadhana Ravikumar, Pulkit Khandelwal, Trevor Glenn, Anica Luther, Sydney Lim, David A. Wolk, Paul A. Yushkevich
Journal: Medical Image Analysis (2022)
Reciprocal interplays between MicroRNAs and pluripotency transcription factors in dictating stemness features in human cancers
Authors: Radhakrishnan Vishnubalaji, Hibah Shaath, Monther Al-Alwan, Essam M. Abdelalim, Nehad M. Alajez
Journal: Seminars in Cancer Biology (2022)

The interplay between microRNAs (miRNAs) and pluripotency transcription factors (TFs) orchestrates the acquisition of cancer stem cell (CSC) features during the course of malignant transformation, rendering them essential cancer cell dependencies and therapeutic vulnerabilities. In this review, we discuss emerging themes in tumor heterogeneity, including the clonal evolution and the CSC models and their implications in resistance to cancer therapies, and then provide thorough coverage on the roles played by key TFs in maintaining normal and malignant stem cell pluripotency and plasticity. In addition, we discuss the reciprocal interactions between miRNAs and MYC, OCT4, NANOG, SOX2, and KLF4 pluripotency TFs and their contributions to tumorigenesis. We provide our view on the potential to interfere with key miRNA-TF networks through the use of RNA-based therapeutics as single agents or in combination with other therapeutic strategies, to abrogate the CSC state and render tumor cells more responsive to standard and targeted therapies.
Multidrug-resistant infection in COVID-19 patients: A meta-analysis
Authors: Siqi Hu, Yao You, Shenghui Zhang, Jiake Tang, Chen Chen, Wen Wen, Chunyi Wang, Yongran Cheng, Mengyun Zhou, Zhanhui Feng, Tao Tan, Guanming Qi, Mingwei Wang, Xiaoyan Liu
Journal: Journal of Infection (2022)
“Double-punch” strategy against triple-negative breast cancer via a synergistic therapy of magneto-mechanical force enhancing NIR-II hypothermal ablation
Authors: Hui Du, Fang Yang, Chenyang Yao, Wenhao Lv, Hao Peng, Stefan G. Stanciu, Harald A. Stenmark, Young Min Song, Bo Jiang, Aiguo Wu
Journal: Biomaterials (2022)
Hybrid and Conventional Endoscopic Submucosal Dissection for Early Gastric Neoplasms: A Multi-Center Randomized Controlled Trial
Authors: Mitsuru Esaki, Eikichi Ihara, Yorinobu Sumida, Hiroyuki Fujii, Shunsuke Takahashi, Kazuhiro Haraguchi, Tsutomu Iwasa, Shinichi Somada, Yosuke Minoda, Haruei Ogino, Koshiro Tagawa, Yoshihiro Ogawa
Journal: Clinical Gastroenterology and Hepatology (2022)

Hybrid endoscopic submucosal dissection (H-ESD), which incorporates endoscopic submucosal dissection (ESD) with endoscopic mucosal resection, has been developed to make ESD technically easier. This study aimed to determine if H-ESD is superior to conventional ESD (C-ESD) for small early gastric neoplasms (EGNs).We conducted a multi-center, prospective, open-label, randomized controlled trial to compare the treatment outcomes of H-ESD and C-ESD (Hybrid-G Trial). Patients with differentiated type intramucosal EGN ≤20 mm in diameter and without ulceration were randomly assigned (1:1) to groups that underwent H-ESD or C-ESD. A single multi-functional snare, SOUTEN (ST1850-20, Kaneka, Medix, Tokyo, Japan), was used for H-ESD. The primary outcome was procedure time. Secondary outcomes included mucosal incision time, time and speed of submucosal dissection, curability, and endoscopic procedural adverse events.A total of 39 and 40 patients underwent H-ESD and C-ESD, respectively. The procedure time of H-ESD was significantly shorter than that of C-ESD (33.16 min vs 62.46 min; H-ESD/C-ESD ratio: 0.53; 95% confidence interval, 0.41-0.69; P < .0001). There was no significant difference in mucosal incision time between the 2 groups; the time and speed of submucosal dissection of H-ESD were significantly shorter than those of C-ESD. No difference was observed between the 2 groups in other outcomes.H-ESD has significantly shorter procedure time than C-ESD, with high and comparable curability and safety for both H-ESD and C-ESD. H-ESD can be a good option for the endoscopic treatment of small EGNs. (UMIN Clinical Trials Registry, Numbers: UMIN000041244).
The dichotomous role of immunoproteasome in cancer: Friend or foe?
Authors: Boya Chen, Haiying Zhu, Bo Yang, Ji Cao
Journal: Acta Pharmaceutica Sinica B (2022)

Immunoproteasome is a variant of proteasome with structural differences in 20S subunits optimizing them for the production of antigenic peptides with higher binding affinity to major histocompatibility complex (MHC)-I molecules. Apart from this primary function in antigen presentation, immunoproteasome is also responsible for the degradation of proteins, both unfolded proteins for the maintenance of protein homeostasis and tumor suppressor proteins contributing to tumor progression. The altered expression of immunoproteasome is frequently observed in cancers; however, its expression levels and effects vary among different cancer types exhibiting antagonistic roles in tumor development. This review focuses on the dichotomous role of immunoproteasome in different cancer types, as well as summarizes the current progression in immunoproteasome activators and inhibitors. Specifically targeting immunoproteasome may be a beneficial therapeutic intervention in cancer treatment and understanding the role of immunoproteasome in cancers will provide a significant therapeutic insight for the prevention and treatment of cancers.
Methylprednisolone for Heart Surgery in Infants — A Randomized, Controlled Trial
Authors: Kevin D. Hill, Prince J. Kannankeril, Jeffrey P. Jacobs, H. Scott Baldwin, Marshall L. Jacobs, Sean M. O’Brien, David P. Bichel, Eric M. Graham, Brian Blasiole, Ashraf Resheidat, Adil S. Husain, S. Ram Kumar, Jerry L. Kirchner, Dianne S. Gallup, Joseph W. Turek, Mark Bleiweis, Bret Mettler, Alexis Benscoter, Eric Wald, Tara Karamlou, Andrew H. Van Bergen, David Overman, Pirooz Eghtesady, Ryan Butts, John S. Kim, John P. Scott, Brett R. Anderson, Michael F. Swartz, Patrick I. McConnell, David F. Vener, Jennifer S. Li
Journal: New England Journal of Medicine (2022)

Although perioperative prophylactic glucocorticoids have been used for decades, whether they improve outcomes in infants after heart surgery with cardiopulmonary bypass is unknown.
Intra-individual comparison of 18F-sodium fluoride PET–CT and 99mTc bone scintigraphy with SPECT in patients with prostate cancer or breast cancer at high risk for skeletal metastases (MITNEC-A1): a multicentre, phase 3 trial
Authors: François Bénard, Sara Harsini, Don Wilson, Katherine Zukotynski, Gad Abikhzer, Eric Turcotte, Mariève Cossette, Ur Metser, Jonathan Romsa, Montgomery Martin, Colin Mar, Fred Saad, Jean-Paul Soucy, Bernhard J Eigl, Peter Black, Andra Krauze, Steven Burrell, Alan Nichol, Jean-Claude Tardif
Journal: The Lancet Oncology (2022)
Air quality and the risk of out-of-hospital cardiac arrest in Singapore (PAROS): a time series analysis
Authors: Andrew Fu Wah Ho, Jamie S Y Ho, Benjamin Yong-Qiang Tan, Seyed Ehsan Saffari, Jun Wei Yeo, Ching-Hui Sia, Meng Wang, Joel Aik, Huili Zheng, Geoffrey Morgan, Wilson Wai San Tam, Wei Jie Seow, Marcus Eng Hock Ong
Journal: The Lancet Public Health (2022)
Hypofractionated, 3-week, preoperative radiotherapy for patients with soft tissue sarcomas (HYPORT-STS): a single-centre, open-label, single-arm, phase 2 trial
Authors: B Ashleigh Guadagnolo, Roland L Bassett, Devarati Mitra, Ahsan Farooqi, Caroline Hempel, Courtney Dorber, Tiara Willis, Wei-Lien Wang, Ravin Ratan, Neeta Somaiah, Robert S Benjamin, Keila E Torres, Kelly K Hunt, Christopher P Scally, Emily Z Keung, Robert L Satcher, Justin E Bird, Patrick P Lin, Bryan S Moon, Valerae O Lewis, Christina L Roland, Andrew J Bishop
Journal: The Lancet Oncology (2022)
Omicron BA.2.75 variant is efficiently neutralised following BA.1 and BA.5 breakthrough infection in vaccinated individuals, Israel, June to September 2022
Authors: Nofar Atari, Limor Kliker, Neta Zuckerman, Bayan Abd Elkader, Yael Weiss-Ottolenghi, Ella Mendelson, Yitshak Kreiss, Gili Regev-Yochay, Michal Mandelboim
Journal: Eurosurveillance (2022)

We evaluated neutralising antibody titres against wild type (WT) SARS-CoV-2 and four Omicron variants (BA.1, BA.2, BA.5 and BA.2.75) in fully vaccinated (three doses of Comirnaty vaccine) healthcare workers (HCW) in Israel who had breakthrough BA.1/BA5 infections. Omicron breakthrough infections in vaccinated individuals resulted in increased neutralising antibodies against the WT and Omicron variants compared with vaccinated uninfected HCW. HCW who recovered from BA.1 or BA.5 infections showed similar neutralising antibodies levels against BA.2.75.
Ongoing toxin-positive diphtheria outbreaks in a federal asylum centre in Switzerland, analysis July to September 2022
Authors: Jacob Kofler, Alban Ramette, Patricia Iseli, Lea Stauber, Jens Fichtner, Sara Droz, Annina Zihler Berner, Anna Bettina Meier, Michelle Begert, Sabine Negri, Anne Jachmann, Peter Michael Keller, Cornelia Staehelin, Barbara Grützmacher
Journal: Eurosurveillance (2022)

Two diphtheria outbreaks occurred in a Swiss asylum center from July to October 2022, one is still ongoing. Outbreaks mainly involved minors and included six symptomatic respiratory diphtheria cases requiring antitoxin. Phylogenomic analyses showed evidence of imported and local transmissions of toxigenic strains in respiratory and skin lesion samples. Given the number of cases (n = 20) and the large genetic diversity accumulating in one centre, increased awareness and changes in public health measures are required to prevent and control diphtheria outbreaks.
mcr-1 colistin resistance gene sharing between Escherichia coli from cohabiting dogs and humans, Lisbon, Portugal, 2018 to 2020
Authors: Juliana Menezes, Joana Moreira da Silva, Sian-Marie Frosini, Anette Loeffler, Scott Weese, Vincent Perreten, Stefan Schwarz, Luís Telo da Gama, Andreia Jesus Amaral, Constança Pomba
Journal: Eurosurveillance (2022)

Background The emergence of colistin resistance is a One Health antimicrobial resistance challenge worldwide. The close contact between companion animals and humans creates opportunities for transmission and dissemination of colistin-resistant bacteria. Aim To detect potential animal reservoirs of colistin-resistant Escherichia coli and investigate the possible sharing of these bacteria between dogs, cats and their cohabiting humans in the community in Lisbon, Portugal. Methods A prospective longitudinal study was performed from 2018 to 2020. Faecal samples from dogs and cats either healthy or diagnosed with a skin and soft tissue or urinary tract infection, and their cohabiting humans were screened for the presence of colistin-resistant E . coli. All isolates were tested by broth microdilution against colistin and 12 other antimicrobials. Colistin-resistant isolates were screened for 30 resistance genes, including plasmid-mediated colistin resistance genes ( mcr-1 to mcr-9 ), and typed by multilocus sequence typing. Genetic relatedness between animal and human isolates was analysed by whole genome sequencing. Results Colistin-resistant E. coli strains harbouring the mcr-1 gene were recovered from faecal samples of companion animals (8/102; 7.8%) and humans (4/125; 3.2%). No difference between control and infection group was detected. Indistinguishable multidrug-resistant E . coli ST744 strains harbouring the mcr-1 gene were found in humans and their dogs in two households. Conclusions The identification of identical E . coli strains containing the plasmid-mediated mcr-1 gene in companion animals and humans in daily close contact is of concern. These results demonstrate the importance of the animal–human unit as possible disseminators of clinically important resistance genes in the community setting.